【摘要】：目的：制備西他沙星注射劑，并對(duì)其進(jìn)行制劑學(xué)、安全性及藥物動(dòng)力學(xué)評(píng)價(jià)。 方法：(1)建立高效液相色譜法測(cè)定西他沙星注射劑中的藥物含量及其有關(guān)物質(zhì)，用來(lái)評(píng)價(jià)制備工藝。(2)西他沙星注射劑的處方設(shè)計(jì)前研究。(3)進(jìn)行西他沙星注射劑的處方篩選及工藝探索。(4)通過(guò)溶血性、過(guò)敏反應(yīng)、血管、肌肉刺激性試驗(yàn)和熱原檢查對(duì)西他沙星注射劑進(jìn)行初步安全性評(píng)價(jià)。(5)選用司帕沙星為內(nèi)標(biāo)物，建立高效液相色譜法測(cè)定大鼠體內(nèi)西他沙星的含量變化，，初步研究其在大鼠體內(nèi)藥動(dòng)學(xué)特征。 結(jié)果：(1)采用HPLC法測(cè)定制劑中西他沙星及有關(guān)物質(zhì)的含量，該法快速、靈敏、穩(wěn)定可靠。(2)西他沙星易溶于酸性水溶液，在高溫條件下穩(wěn)定性良好；對(duì)酸、堿、高濕及光照條件敏感，該藥物的最穩(wěn)定pH約為4~6之間。(3)以乳酸為pH調(diào)節(jié)劑，氯化鈉為等滲調(diào)節(jié)劑成功制備了西他沙星注射劑。制劑工藝為采用0.03%活性炭于煮沸條件下處理30min，滅菌條件為115℃滅菌30min。(4)注射劑經(jīng)過(guò)影響因素、加速、長(zhǎng)期試驗(yàn)各指標(biāo)均符合規(guī)定，制劑質(zhì)量穩(wěn)定。(5)安全性評(píng)價(jià)表明，制備的西他沙星注射劑溶血性、過(guò)敏反應(yīng)、血管及肌肉刺激性和熱原檢查均顯陰性。(6)西他沙星注射劑大鼠體內(nèi)藥動(dòng)學(xué)研究表明，藥物在大鼠體內(nèi)t1/2為0.857h，平均滯留時(shí)間(MRT)為0.996h，表觀分布容積為4.140L·kg-1。 結(jié)論：成功建立了西他沙星注射劑的制備方法，并得到良好的初步穩(wěn)定性及安全性評(píng)價(jià)結(jié)果。西他沙星注射劑的大鼠體內(nèi)藥動(dòng)學(xué)研究結(jié)果為進(jìn)一步研發(fā)奠定了良好的基礎(chǔ)。
[Abstract]:Objective: to prepare cilafloxacin injection and evaluate its pharmacokinetics and safety. Methods: (1) to establish a high performance liquid chromatography (HPLC) method for the determination of cetafloxacin injection and its related substances. It was used to evaluate the preparation process. (2) Pre-design study on the formulation of cilafloxacin injection. (3) screening of the formulation of cilastacin injection and exploration of the technology. (4) by hemolytic, allergic reaction, blood vessel, blood vessel, Muscle irritation test and pyrogen test were used to evaluate the safety of cisfloxacin injection. (5) using sparfloxacin as internal standard, a high performance liquid chromatography (HPLC) method was established for the determination of cetafloxacin in rats. The pharmacokinetic characteristics in rats were preliminarily studied. Results: (1) the HPLC method was used to determine the content of estracin and its related substances. The method was rapid, sensitive, stable and reliable. (2) ciltafloxacin was easily soluble in acidic aqueous solution and had good stability at high temperature. The most stable pH of the drug was about 4 ~ 6. (3) Cetafloxacin injection was successfully prepared with lactic acid as pH regulator and sodium chloride as isoosmotic regulator. The preparation process was treated with 0.03% activated carbon for 30 min under boiling condition, and sterilizing condition was 115 鈩

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